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acetaminophen in patients with acute postoperative pain: a randomized controlled trial
Abstracts
(412) Treatment effects of opioids versus NSAIDs prescribed from the emergency department following motor vehicle collision: the impact on pain outcomes at 6 weeks F Beaudoin, R Gutman, D Peak, J Jones, R Swor, R Domeier, D Lee, N Rathlev, P Hendry, and S McLean; Alpert Medical School of Brown University, Providence, RI
The Journal of Pain
S79
(414) Time to onset of pain relief with biphasic immediaterelease/extended-release hydrocodone bitartrate/acetaminophen in patients with acute postoperative pain: a randomized controlled trial Y Zheng, R Margulis, K Kostenbader, and T Barrett; Lotus Clinical Research, LLC, Pasadena, CA
More than four million Americans present to U.S. Emergency Departments (EDs) each year after motor vehicle collision (MVC). More than 90% of these individuals have acute musculoskeletal pain (MSP), and, while less than 5% have a fracture or require hospital admission, 20-30% transition to chronic MSP. Individuals with acute MSP after MVC are most often discharged with oral nonsteroidal anti-inflammatory drugs (NSAIDs) or opioid medications, however optimal medication treatments are poorly defined and the influence of acute medication choices on post-MVC pain trajectory are unknown. In this study we evaluated the effect of opioid versus NSAID medication treatment at the time of ED discharge on the presence of moderate or severe MSP (MSMSP, NRS > 3) six weeks after MVC. Data was obtained from a large prospective cohort of adult European Americans (n=948) who presented to the ED after MVC. Propensity score matched analysis was used to compare the odds of MSMSP at six week follow-up (obtained in 859/948 (91%) among patients discharged with opioid analgesics alone (198/859 (23%)) vs. those discharged with NSAIDs alone (338/859 (39%)). Participants were propensity-matched on demographic and clinical characteristics, baseline pain scores, and MVC characteristics. At 6weeks, 49% of those receiving NSAIDS and 56% of those receiving opioids reported MSMSP. After propensity matching, there was no significant difference in MSMSP at six weeks between those discharged with opioids vs. those discharged with NSAIDS (OR=0.92; 95% CI 0.33 – 1.51). These results suggest that initial ED provider choice of NSAIDs versus opioid medication at discharge following MVC does not influence the development of MSMSP six weeks after MVC. Supported by NIAMS R01AR056328.
To ideally manage postoperative pain, clinicians require an analgesic that provides rapid onset and steady plasma levels. Current immediate-release (IR) and extended-release (ER) opioid formulations fail to meet these criteria. Biphasic IR/ER opioid analgesics are intended to provide rapid onset of relief and prolonged duration of analgesia. This randomized, doubleblind, placebo-controlled trial investigated the time to onset of analgesia with biphasic hydrocodone/acetaminophen (IR/ER HB/APAP; MNK-155, Mallinckrodt Pharmaceuticals, Hazelwood, MO) in patients with moderate to severe acute postoperative pain. Patients (N=403) received IR/ER HB/APAP 7.5/ 325 mg as a 3-tablet initial dose (total dose 22.5/975 mg) followed by 2 tablets (15/650 mg total dose) every 12 hours or matching placebo for 48 hours following unilateral bunionectomy. A blinded stop watch method was used to measure the time to perceptible, meaningful, and confirmed pain relief. Results were analyzed using Kaplan-Meier methods and a log-rank test. Data for patients who used rescue medication (ibuprofen) before onset of relief were censored. Compared with placebo, IR/ER HB/APAP was associated with shorter median times to perceptible (34.42 min vs 56.70, respectively; P<0.001), meaningful (118.60 min vs not estimable, respectively; P<0.001), and confirmed perceptible pain relief (55.40 min vs not estimable, respectively; P<0.001). Data censoring due to use of rescue medication was twice as frequent with placebo versus IR/ER HB/APAP. Thus, IR/ER HB/APAP 7.5/ 325-mg administered in an initial 3-tablet dose followed by 2 tablet doses every 12 hours provided rapid relief of acute postoperative pain. Results from this study support the efficacy of IR/ER HB/APAP for postoperative pain; further research is required to assess efficacy, safety, and patient satisfaction with active comparators. This research was supported by Mallinckrodt.
(413) Adolescents’ home pain management after laparoscopic appendectomy
(415) Time to onset of pain relief with biphasic immediaterelease/extended-release oxycodone/acetaminophen in patients with acute postoperative pain: a randomized controlled trial
L Karamessinis, R Manworren, A Pantaleao, and J Cooper; Connecticut Children’s Medical Center, Hartford, CT The purpose of this study is to describe children’s pain experiences and home analgesic use after laparoscopic appendectomy. Patients (n=93, mean age 14.26 years, SD=1) were prescribed 5-45 pills (mean 15) of oxycodone/acetaminophen (75.3%), hydrocodone/acetaminophen (16.1%), or oxycodone (7.5%). Patients were asked to complete a 14-day pain diary; and their prescription opioid analgesics (pills) were dispensed with eCAPTM technology. Diary and eCAPTM data was returned by 39 patients, 10 provided partial data (4 eCAPTM, 6 diaries), and 23 failed to schedule or show up for their post-operative visit. Of those who returned diary data (n=45), all except one reported pain the first partial day home after discharge (mean=3.41, SD=0.82), with 16 reporting scores of 4 or 5 of 5 (Wong-Baker FACES pain scale). Almost half (n=20) were still reporting pain on day 7, with 1 reporting the high score of 4; and 7 patients were still reporting pain on day 14, with 1 reporting the high score of 3 that day. Patients used a mean of 5.81 pills by pill count (0 to 20) and diary report (0 to 24). There were 5 patients who reported not using any pills at home. Most (n=34) patients took a pill on the first partial day home, with only 3 patients continuing to report use on day 7. No patients reported taking a pill in their diary after the 10th day home after discharge. Of 749 opioid analgesic pills prescribed to 49 patients who reported partial or complete data, 689 pills were dispensed, 167.5 pills (24.31%) were reportedly used for the reason prescribed, 53.5 pills (7.76%) were unaccounted for by pill count, and 468 pills (67.92%) were returned to families for their disposal. Supported by a grant from Nurse Practitioner Health Foundation and reduced pricing for eCAPsTM from Information Mediary Corporation.
N Singla, L Sisk, K Kostenbader, and J Young; Lotus Clinical Research, LLC, Pasadena, CA Acute postoperative pain requires rapid onset of analgesia but prolonged duration of analgesia also provides benefit. Transition from perioperative intravenous analgesics to oral analgesics involves use of immediate-release (IR) opioids offering rapid onset of relief but requiring frequent dosing. Lessfrequent dosing may improve sleep or stability of pain control; however, few trials have assessed extended-release (ER) formulations in postoperative pain because of their delayed onset of analgesia. Biphasic IR/ER opioids may permit rapid onset and less-frequent dosing. This analysis of data from a randomized, double-blind study assessed time to onset of pain relief with biphasic IR/ER oxycodone/acetaminophen (IR/ER OC/APAP; XartemisÔ XR, Mallinckrodt Brand Pharmaceuticals, Inc., Hazelwood, MO) in patients with acute postoperative pain following unilateral bunionectomy. In patients (N=303) who received IR/ ER OC/APAP 7.5/325 mg (2 tablets, total dose 15/650 mg) or placebo every 12 hours for 48 hours, time to perceptible, meaningful, and confirmed pain relief was measured using a validated double stopwatch method. Data for patients who used rescue medication (ibuprofen 400 mg every 4 hours as needed) before onset of relief were censored. Outcomes were estimated using Kaplan-Meier methods and analyzed using the log-rank test. Compared with placebo, IR/ER OC/APAP was associated with shorter median times to perceptible (33.56 vs 43.63 min, respectively; P=0.002), meaningful (92.25 min vs not estimable; P<0.001), and confirmed pain relief (47.95 min vs not estimable; P<0.001). Data censoring due to rescue medication use was twice as frequent with placebo. Thus, IR/ER OC/APAP provided more rapid pain relief compared with placebo. The only published, similarly-designed study of an ER formulation (oxymorphone ER) reported onset of meaningful pain relief in a median time of 183 minutes. These results suggest that IR/ER OC/APAP provides rapid onset of relief with twice-daily dosing. This research was supported by Mallinckrodt.
(412) Treatment effects of opioids versus NSAIDs prescribed from the emergency department following motor vehicle collision: the impact on pain outcomes at 6 weeks F Beaudoin, R Gutman, D Peak, J Jones, R Swor, R Domeier, D Lee, N Rathlev, P Hendry, and S McLean; Alpert Medical School of Brown University, Providence, RI
The Journal of Pain
S79
(414) Time to onset of pain relief with biphasic immediaterelease/extended-release hydrocodone bitartrate/acetaminophen in patients with acute postoperative pain: a randomized controlled trial Y Zheng, R Margulis, K Kostenbader, and T Barrett; Lotus Clinical Research, LLC, Pasadena, CA
More than four million Americans present to U.S. Emergency Departments (EDs) each year after motor vehicle collision (MVC). More than 90% of these individuals have acute musculoskeletal pain (MSP), and, while less than 5% have a fracture or require hospital admission, 20-30% transition to chronic MSP. Individuals with acute MSP after MVC are most often discharged with oral nonsteroidal anti-inflammatory drugs (NSAIDs) or opioid medications, however optimal medication treatments are poorly defined and the influence of acute medication choices on post-MVC pain trajectory are unknown. In this study we evaluated the effect of opioid versus NSAID medication treatment at the time of ED discharge on the presence of moderate or severe MSP (MSMSP, NRS > 3) six weeks after MVC. Data was obtained from a large prospective cohort of adult European Americans (n=948) who presented to the ED after MVC. Propensity score matched analysis was used to compare the odds of MSMSP at six week follow-up (obtained in 859/948 (91%) among patients discharged with opioid analgesics alone (198/859 (23%)) vs. those discharged with NSAIDs alone (338/859 (39%)). Participants were propensity-matched on demographic and clinical characteristics, baseline pain scores, and MVC characteristics. At 6weeks, 49% of those receiving NSAIDS and 56% of those receiving opioids reported MSMSP. After propensity matching, there was no significant difference in MSMSP at six weeks between those discharged with opioids vs. those discharged with NSAIDS (OR=0.92; 95% CI 0.33 – 1.51). These results suggest that initial ED provider choice of NSAIDs versus opioid medication at discharge following MVC does not influence the development of MSMSP six weeks after MVC. Supported by NIAMS R01AR056328.
To ideally manage postoperative pain, clinicians require an analgesic that provides rapid onset and steady plasma levels. Current immediate-release (IR) and extended-release (ER) opioid formulations fail to meet these criteria. Biphasic IR/ER opioid analgesics are intended to provide rapid onset of relief and prolonged duration of analgesia. This randomized, doubleblind, placebo-controlled trial investigated the time to onset of analgesia with biphasic hydrocodone/acetaminophen (IR/ER HB/APAP; MNK-155, Mallinckrodt Pharmaceuticals, Hazelwood, MO) in patients with moderate to severe acute postoperative pain. Patients (N=403) received IR/ER HB/APAP 7.5/ 325 mg as a 3-tablet initial dose (total dose 22.5/975 mg) followed by 2 tablets (15/650 mg total dose) every 12 hours or matching placebo for 48 hours following unilateral bunionectomy. A blinded stop watch method was used to measure the time to perceptible, meaningful, and confirmed pain relief. Results were analyzed using Kaplan-Meier methods and a log-rank test. Data for patients who used rescue medication (ibuprofen) before onset of relief were censored. Compared with placebo, IR/ER HB/APAP was associated with shorter median times to perceptible (34.42 min vs 56.70, respectively; P<0.001), meaningful (118.60 min vs not estimable, respectively; P<0.001), and confirmed perceptible pain relief (55.40 min vs not estimable, respectively; P<0.001). Data censoring due to use of rescue medication was twice as frequent with placebo versus IR/ER HB/APAP. Thus, IR/ER HB/APAP 7.5/ 325-mg administered in an initial 3-tablet dose followed by 2 tablet doses every 12 hours provided rapid relief of acute postoperative pain. Results from this study support the efficacy of IR/ER HB/APAP for postoperative pain; further research is required to assess efficacy, safety, and patient satisfaction with active comparators. This research was supported by Mallinckrodt.
(413) Adolescents’ home pain management after laparoscopic appendectomy
(415) Time to onset of pain relief with biphasic immediaterelease/extended-release oxycodone/acetaminophen in patients with acute postoperative pain: a randomized controlled trial
L Karamessinis, R Manworren, A Pantaleao, and J Cooper; Connecticut Children’s Medical Center, Hartford, CT The purpose of this study is to describe children’s pain experiences and home analgesic use after laparoscopic appendectomy. Patients (n=93, mean age 14.26 years, SD=1) were prescribed 5-45 pills (mean 15) of oxycodone/acetaminophen (75.3%), hydrocodone/acetaminophen (16.1%), or oxycodone (7.5%). Patients were asked to complete a 14-day pain diary; and their prescription opioid analgesics (pills) were dispensed with eCAPTM technology. Diary and eCAPTM data was returned by 39 patients, 10 provided partial data (4 eCAPTM, 6 diaries), and 23 failed to schedule or show up for their post-operative visit. Of those who returned diary data (n=45), all except one reported pain the first partial day home after discharge (mean=3.41, SD=0.82), with 16 reporting scores of 4 or 5 of 5 (Wong-Baker FACES pain scale). Almost half (n=20) were still reporting pain on day 7, with 1 reporting the high score of 4; and 7 patients were still reporting pain on day 14, with 1 reporting the high score of 3 that day. Patients used a mean of 5.81 pills by pill count (0 to 20) and diary report (0 to 24). There were 5 patients who reported not using any pills at home. Most (n=34) patients took a pill on the first partial day home, with only 3 patients continuing to report use on day 7. No patients reported taking a pill in their diary after the 10th day home after discharge. Of 749 opioid analgesic pills prescribed to 49 patients who reported partial or complete data, 689 pills were dispensed, 167.5 pills (24.31%) were reportedly used for the reason prescribed, 53.5 pills (7.76%) were unaccounted for by pill count, and 468 pills (67.92%) were returned to families for their disposal. Supported by a grant from Nurse Practitioner Health Foundation and reduced pricing for eCAPsTM from Information Mediary Corporation.
N Singla, L Sisk, K Kostenbader, and J Young; Lotus Clinical Research, LLC, Pasadena, CA Acute postoperative pain requires rapid onset of analgesia but prolonged duration of analgesia also provides benefit. Transition from perioperative intravenous analgesics to oral analgesics involves use of immediate-release (IR) opioids offering rapid onset of relief but requiring frequent dosing. Lessfrequent dosing may improve sleep or stability of pain control; however, few trials have assessed extended-release (ER) formulations in postoperative pain because of their delayed onset of analgesia. Biphasic IR/ER opioids may permit rapid onset and less-frequent dosing. This analysis of data from a randomized, double-blind study assessed time to onset of pain relief with biphasic IR/ER oxycodone/acetaminophen (IR/ER OC/APAP; XartemisÔ XR, Mallinckrodt Brand Pharmaceuticals, Inc., Hazelwood, MO) in patients with acute postoperative pain following unilateral bunionectomy. In patients (N=303) who received IR/ ER OC/APAP 7.5/325 mg (2 tablets, total dose 15/650 mg) or placebo every 12 hours for 48 hours, time to perceptible, meaningful, and confirmed pain relief was measured using a validated double stopwatch method. Data for patients who used rescue medication (ibuprofen 400 mg every 4 hours as needed) before onset of relief were censored. Outcomes were estimated using Kaplan-Meier methods and analyzed using the log-rank test. Compared with placebo, IR/ER OC/APAP was associated with shorter median times to perceptible (33.56 vs 43.63 min, respectively; P=0.002), meaningful (92.25 min vs not estimable; P<0.001), and confirmed pain relief (47.95 min vs not estimable; P<0.001). Data censoring due to rescue medication use was twice as frequent with placebo. Thus, IR/ER OC/APAP provided more rapid pain relief compared with placebo. The only published, similarly-designed study of an ER formulation (oxymorphone ER) reported onset of meaningful pain relief in a median time of 183 minutes. These results suggest that IR/ER OC/APAP provides rapid onset of relief with twice-daily dosing. This research was supported by Mallinckrodt.